From physiology to pathology: Emerging roles of GPER in cardiovascular disease

Cardiovascular diseases (CVDs) are among the leading causes of death globally and pose a significant threat to public health. Factors such as prolonged high cholesterol levels, diabetes, smoking, unhealthy diet, and genetic predisposition could contribute to the occurrence and development of CVDs. Common CVDs include hypertension (HTN), atherosclerosis (AS), myocardial infarction (MI), myocardial ischemia-reperfusion injury (MIRI), heart failure (HF) and arrhythmia. Estrogen is recognized for its cardiovascular protective effects, resulting in lower incidence and mortality rates of CVDs in premenopausal women compared to men. The G protein- coupled estrogen receptor (GPER), a G protein-coupled receptor with a seven-transmembrane structure, exhibits unique structural characteristics and widespread tissue distribution. GPER activates intracellular signaling pathways through its interaction with G proteins, mediating estrogen's biological effects and participating in the regulation of cardiovascular function, metabolic balance, and nervous system. Although recent research has highlighted the significant role of GPER in the cardiovascular system, its specific mechanisms remain unclear. Therefore, this review summarizes the latest research on GPER in CVDs, including its fundamental characteristics, physiological functions in the cardiovascular system, and its roles and potential therapeutic applications incommon CVDs such as HTN, AS, MI, MIRI, HF and arrhythmia. Exploring GPER's positive effects on cardiovascular health will provide new strategies and research directions for the treatment of CVDs. (c) 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar tech- nologies.